The objective of our research program is to investigate ultrashort pulsed laser tissue interaction in the picosecond and femtosecond regime. Our goals are threefold: We will investigate laser tissue effects using both biological and model system. We will develop and apply novel time resolved techniques to study the dynamics of tissue response after laser energy deposition as well as the picosecond and femtosecond behavior associated with the primary absorption of energy. Finally, we will develop approaches to control laser tissue interactions and selectively enhance desired therapeutic effects. We will focus on two major types of clinically important ultrashort pulse laser tissue interaction: ablation and laser induced breakdown. 1. We will investigate ablation produced by high intensity femtosecond pulses. Our preliminary results demonstrate ablation of the cornea using visible wavelengths. This new type of laser tissue interaction produces highly localized incisions with characteristics similar to ultraviolet ablation but affords the possibility of treating internal structures and using endoscopic delivery. We will investigate ablation thresholds, rates, and morphology in model polymer system and biological systems such as the cornea and the anterior eye in vitro and in vivo. Femtosecond time resolved techniques will be develope and applied to investigate physical mechanisms. 2. We will investigate optical breakdown using high intensity picosecond and femtosecond pulses. Studies will be performed in simple models such as saline as well as in the cornea and anterior eye. We will develop time resolved techniques to investigate plasma absorption, acoustic wave generation, and cavitation associated with the breakdown. We will explore the use of different pulse durations and novel time domain exposure techniques to selectively enhance desired tissue effects and yield a microsurgical precision. 3. Finally, we will develop a novel laser source which produces tunable pulse durations in the picosecond and femtosecond range. This laser will be used for studies of both ablation and breakdown in model as we)l as biological systems including the cornea and the retina to quantify the effects of pulse duration in laser tissue interaction. We believe that high intensity picosecond and femtosecond lasers and new exposure techniques can produce tissue effects which are a hybrid between existing ultraviolet ablation and laser induced breakdown. The optimization of high intensity laser tissue interaction may thus provide microsurgical capability while permitting the treatment of internal structures and allowing endoscopic delivery.